HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway
HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway
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DOI：
10.1002/j.1460-2075.1996.tb01093.x
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发表时间：
1996-12-16
期刊：
影响因子：
11.4
通讯作者：
Iscove, NN
中科院分区：
文献类型：
--
作者：
Kiefer, F;Tibbles, LA;Iscove, NN
在哺乳动物细胞中，特异性应激激活蛋白激酶（SAPK/JNK）途径响应于炎性细胞因子、热损伤、化疗药物和UV或电离辐射而被激活。在不同的组织中，这些刺激与SAPK/JNK通路激活的联系机制仍有待确定。我们已经开发并应用了一种基于PCR的减法策略来识别在造血的特定发育点差异表达的新基因。我们发现，这样一个基因，造血祖细胞激酶1（hpk 1），编码丝氨酸/苏氨酸激酶共享相似的激酶结构域的Ste 20。HPK 1在转染入COS 1细胞后特异性激活SAPK/JNK通路，但不刺激p38/RK或促分裂原激活的ERK信号通路。SAPK的激活需要功能性HPK 1激酶结构域，并且HPK 1经由含SH 3的混合谱系激酶MLK-3和已知的SAPK激活剂SEK 1发出信号。因此，HPK 1提供了一个细胞类型特异性输入SAPK/JNK途径的例子。其表达的发育特异性表明在造血谱系决定和生长调节中的潜在作用。
In mammalan cells, a specific stress-activated protein kinase (SAPK/JNK) pathway is activated in response to inflammatory cytokines, injury from heat, chemotherapeutic drugs and UV or ionizing radiation. The mechanisms that link these stimuli to activation of the SAPK/JNK pathway in different tissues remain to be identified. We have developed and applied a PCR-based subtraction strategy to identify novel genes that are differentially expressed at specific developmental points in hematopoiesis. We show that one such gene, hematopoietic progenitor kinase 1 (hpk1), encodes a serine/threonine kinase sharing similarity with the kinase domain of Ste20. HPK1 specifically activates the SAPK/JNK pathway after transfection into COS1 cells, but does not stimulate the p38/RK or mitogen-activated ERK signaling pathways. Activation of SAPK requires a functional HPK1 kinase domain and HPK1 signals via,the SH3-containing mixed lineage kinase MLK-3 and the known SAPK activator SEK1. HPK1 therefore provides an example of a cell type-specific input into the SAPK/JNK pathway. The developmental specificity of its expression suggests a potential role in hematopoietic lineage decisions and growth regulation.